Oxidation of isoniazid by N-haloarenesulfonamidates in alkaline medium: A kinetic and mechanistic study

The kinetics of oxidation of Isoniazid (INH) by sodium N-haloarenesulfonamidates. chloramine-T (CAT), bromamine-T (BAT), chloramine-B (CAB), and bromamine-B (BAB), has been studied in alkaline medium at 303 K. The oxidation reaction follows identical kinetics with a first-order dependence on each [oxidant] and [INH] and an inverse fractional-order on [OH-]. Addition of the reaction product (p-toluenesulfonamide or benzenesulfonamide) had no significant effect on the reaction rate. Variation of ionic strength and addition of halide ions have no influence on the rate. There is a negative effect of dielectric constant of the solvent. Studies of solvent isotope effects using D2O showed a retardation of rate in the heavier medium. The reaction was studied at different temperatures, and activation parameters have been computed from the Arrhenius and Eyring plots. Isonicotinic acid was identified as the oxidation product by GC-MS. A two-pathway mechanism is proposed in which RNHX and the anion RNX- interact with the substrate in the rate-limiting steps. The mechanism proposed and the derived rate laws are consistent with the observed kinetics. The rate of oxidation of INH increases in the order: BAT > BAB > CAT > CAB. This effect is mainly due to electronic factors. (C) 2000 John Wiley & Sons, Inc.